Wildfire is a major concern worldwide and particularly in Australia. The 2019–2020 wildfires in Australia became historically significant as they were widespread and extremely severe. Linking climate and vegetation settings to wildfires can provide insightful information for wildfire prediction, and help better understand wildfires behavior in the future. The goal of this research was to examine the relationship between the recent wildfires, various hydroclimatological variables, and satellite-retrieved vegetation indices. The analyses performed here show the uniqueness of the 2019–2020 wildfires. The near-surface air temperature from December 2019 to February 2020 was about 1 °C higher than the 20-year mean, which increased the evaporative demand. The lack of precipitation before the wildfires, due to an enhanced high-pressure system over southeast Australia, prevented the soil from having enough moisture to supply the demand, and set the stage for a large amount of dry fuel that highly favored the spread of the fires.

The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.

Monoamine oxidase B inhibitory activity is closely regulated by the interaction of the small molecules with the enzyme. It is therefore desirable to use theoretical approaches to design rational methods to develop new molecules to modulate specific interactions with the protein. Here, we report such methods, and we illustrate their successful implementation by studying six synthetized 3-arylcoumarins (71–76) based on them. Monoamine oxidase B inhibition is essential to maintain the balance of dopamine, and one of its major functions is to combat dopamine degradation, a phenomenon linked to Parkinson's disease. In this work, we study small-molecule inhibitors based on the 3-arylcoumarin scaffold and their monoamine oxidase B selective inhibition. We show that 3D-QSAR models, in particular CoMFA and CoMSIA, and molecular docking approaches, enhance the probability to find new interesting inhibitors, avoiding very costly and time-consuming synthesis and biological evaluations.

ABSTRACT The existence of mutually correlated thin and rotating planes of satellite galaxies around both the Milky Way (MW) and Andromeda (M31) calls for an explanation. Previous work in Milgromian dynamics (MOND) indicated that a past MW–M31 encounter might have led to the formation of these satellite planes. We perform the first-ever hydrodynamical MOND simulation of the Local Group using phantom of ramses. We show that an MW–M31 encounter at z ≈ 1, with a perigalactic distance of about 80 kpc, can yield two disc galaxies at z = 0 oriented similarly to the observed galactic discs and separated similarly to the observed M31 distance. Importantly, the tidal debris are distributed in phase space similarly to the observed MW and M31 satellite planes, with the correct preferred orbital pole for both. The MW–M31 orbital geometry is consistent with the presently observed M31 proper motion despite this not being considered as a constraint when exploring the parameter space. The mass of the tidal debris around the MW and M31 at z = 0 compare well with the mass observed in their satellite systems. The remnant discs of the two galaxies have realistic radial scale lengths and velocity dispersions, and the simulation naturally produces a much hotter stellar disc in M31 than in the MW. However, reconciling this scenario with the ages of stellar populations in satellite galaxies would require that a higher fraction of stars previously formed in the outskirts of the progenitors ended up within the tidal debris, or that the MW–M31 interaction occurred at z > 1.

The study of binding site similarities can be relevant to understand the interaction of different drugs at several molecular targets. The increasing availability of protein crystal structures and the development of novel algorithms designed to evaluate three-dimensional similarities, represent a great opportunity to explore the existence of electronic and shape features shared by clinically relevant proteins, which could assist drug design and discovery. Proteins involved in the recognition of monoaminergic neurotransmitters, such as monoamine transporters or monoamine oxidases (MAO) have been related to several psychiatric and neurological disorders such as depression or Parkinson's disease. In this work, we evaluated the possible existence of similarities among the binding sites of the serotonin transporter (SERT), the dopamine transporter (DAT), MAO-A and MAO-B. This study was carried out using molecular simulation methodologies linked to the statistical algorithm PocketMatch, which was modified in order to obtain similarities profiles. Our results show that DAT and SERT exhibit a high degree of 3-D similarities all along the pathway that is presumably involved in the substrate transport process. Distinct differences, on the other hand, were found both at the extracellular and the intracellular ends of the transporters, which might be involved in the selective initial recognition of the corresponding substrate. Similarities were also found between the active (catalytic) site of MAO-A and the extracellular vestibule of SERT (the S2 binding site). These results suggest some degree of structural convergence for these proteins, which have different functions, tissue distribution and genetic origin, but which share the same endogenous ligand (serotonin). Beyond the functional implications, these findings are valuable for the design of both selective and non-selective ligands.

Background/Objectives: Bcr-Abl inhibitors such as imatinib have been used to treat chronic myeloid leukemia (CML). However, the efficacy of these drugs has diminished due to mutations in the kinase domain, notably the T315I mutation. Therefore, in this study, new purine derivatives were designed as Bcr-Abl inhibitors based on 3D-QSAR studies. Methods: A database of 58 purines that inhibit Bcr-Abl was used to construct 3D-QSAR models. Using chemical information from these models, a small group of new purines was designed, synthesized, and evaluated in Bcr-Abl. Viability assays were conducted on imatinib-sensitive CML cells (K562 and KCL22) and imatinib-resistant cells (KCL22-B8). In silico analyses were performed to confirm the results. Results: Seven purines were easily synthesized (7a–g). Compounds 7a and 7c demonstrated the highest inhibition activity on Bcr-Abl (IC50 = 0.13 and 0.19 μM), surpassing the potency of imatinib (IC50 = 0.33 μM). 7c exhibited the highest potency, with GI50 = 0.30 μM on K562 cells and 1.54 μM on KCL22 cells. The GI50 values obtained for non-neoplastic HEK293T cells indicated that 7c was less toxic than imatinib. Interestingly, KCL22-B8 cells (expressing Bcr-AblT315I) showed greater sensitivity to 7e and 7f than to imatinib (GI50 = 13.80 and 15.43 vs. >20 μM, respectively). In silico analyses, including docking and molecular dynamics studies of Bcr-AblT315I, were conducted to elucidate the enhanced potency of 7e and 7f. Thus, this study provides in silico models to identify novel inhibitors that target a kinase of significance in CML.

ABSTRACT We present a high signal-to-noise (SNR $\sim$ 450), high-dispersion ($R \equiv \lambda / \Delta \lambda \sim$ 28 000) $H$- and $K$-band spectroscopic atlas of the L7.5 and T0.5 components of the Luhman 16AB binary (WISE J104915.57$-$531906.1AB): the closest pair of brown dwarfs, and one of the best substellar benchmarks. The spectra were combined from a 70-d spectroscopic monitoring campaign of the binary with IGRINS on Gemini South. We fit model photospheres to the combined high-quality spectra to estimate atmospheric parameters. The model is based on the Sonora model atmosphere further incorporating the effects of clouds and disequilibrium. We detect ammonia (NH3) lines in both binary components, making Luhman 16A the warmest object where individual NH3 lines were identified. We discover hydrogen (H2), hydrogen sulfide (H2S), and hydrogen fluoride (HF) lines in both components, following recent reports of these species in either cooler (H2, H2S in a T6 dwarf) or warmer (HF in young late-M or mid-L dwarfs) objects. Methane (CH4) shows a small contribution, with lines sensitive to the slight temperature difference spanning the L/T transition. Against model expectations, we do not detect FeH lines, implying more efficient iron rainout than incorporated in the models. We find various unidentified features in water-dominated regions, likely the result of residual inaccuracies in the water line lists. We searched for planetary-mass companions by periodogram analysis of radial velocities over 70 d but detected no significant signal. The upper limits of projected planetary mass are $M\sin {i}=$ 0.2 $M_{\mathrm{J}}$ and 0.3 $M_{\mathrm{J}}$ at P $\sim$ 1 d, and 0.4 $M_{\mathrm{J}}$ and 0.7 $M_{\mathrm{J}}$ at P $\sim$ 10 d for Luhman 16A and B, respectively.

We present the first volume-limited sample of spectroscopically confirmed hot subluminous stars out to 500 pc, defined using the accurate parallax measurements from the Gaia space mission data release 3 (DR3). The sample comprises a total of 397 members, with 305 (~77%) identified as hot subdwarf stars, including 83 newly discovered systems. Of these, we observe that 178 (~58%) are hydrogen-rich sdBs, 65 are sdOBs (~21%), 32 are sdOs (~11%), and 30 are He-sdO/Bs (~10%). Among them, 48 (~16%) exhibit an infrared excess in their spectral energy distribution fits, suggesting a composite binary system. The hot subdwarf population is estimated to be 90% complete, assuming that most missing systems are these composite binaries located within the main sequence (MS) in the Gaia colour-magnitude diagram. The remaining sources in the sample include cataclysmic variables, blue horizontal branch stars, hot white dwarfs, and MS stars. We derived the mid-plane density ρ 0 and scale height h z for the non-composite hot subdwarf star population using a hyperbolic sechant profile (sech 2 ). The best-fit values are ρ 0 = 5.17 ± 0.33 × 10 −7 stars pc −3 and h z = 281 ± 62 pc. When accounting for the composite-colour hot subdwarfs and their estimated completeness, the mid-plane density increases to ρ 0 = 6.15 −0.53 +1.16 × 10 −7 stars pc −3 . This corrected space density is an order of magnitude lower than predicted by population synthesis studies, supporting previous observational estimates.

Context. Classical Be stars are rapidly rotating B-type stars exhibiting Balmer emission lines originating from circumstellar Keplerian gaseous disks, which likely form through episodic mass-ejection events. The currently favored model for Be star disks is the viscous decretion disk (VDD) model. However, the mechanism behind the mass ejection process during the formation of a VDD is a mystery. Aims. We present peculiar behavior of the Be star KIC 9715425, which exhibited several minor outbursts (MIBs) and one major outburst (MAB) observed as brightenings in broadband photometry, as well as transient Hα line emission. The variability may provide valuable keys to understanding the nature of Be outbursts. Methods. Based on Kepler, the All-Sky Automated Survey for Supernovae (ASAS-SN) and the Transiting Exoplanet Survey Satellite time-series photometry, the Large Sky Area Multi-Object Fiber Spectroscopic Telescope spectroscopy, multi-wavelength observations in the near-ultraviolet (NUV) from the Galaxy Evolution Explorer (GALEX) and optical from Gaia, Xinglong 2.16 m telescope and Isaac Newton Telescope of KIC 9715425 covering its outbursts, we determined fundamental parameters of the central star and the circumstellar disk. A frequency analysis and spectral modeling were carried out to characterize the events. Results. During the major outburst, we find a 36% flux increase in the GALEX NUV band compared to 25% in the Kepler band, suggesting that whatever produced the flux increase should be hotter than the central B-type star. This is contradictory to the conventional scenario that the VDD should be cooler. In addition, such a high flux increase can only be accounted for by a luminous disk, which should produce a much stronger Hα emission than observed. The origin of this anomalously hot component remains unexplained. Conclusions. Except for the bluing, the available observations of KIC 9715425 are perfectly compatible with being a normal Be star. If the bluing was physically related to the MAB, the most economical effort to identify the nature of the underlying process could be adaptive NUV and far-ultraviolet monitoring of Be stars with cyclically repeating MABs.

We introduce an algebra of braids and ties (or bt-algebra) of type B. In analogy to the construction of the bt-algebra of type A, we define this bt–algebra of type B through a framization of the Hecke algebra of type B. We find a basis for it, a faithful tensorial representation, and we prove that it supports a Markov trace, from which we derive invariants of classical links in the solid torus.

Abstract Aims Dynamin‐2 is a large GTPase, a member of the dynamin superfamily that regulates membrane remodelling and cytoskeleton dynamics. Mutations in the dynamin‐2 gene ( DNM2 ) cause autosomal dominant centronuclear myopathy (CNM), a congenital neuromuscular disorder characterised by progressive weakness and atrophy of the skeletal muscles. Cognitive defects have been reported in some DNM2 ‐linked CNM patients suggesting that these mutations can also affect the central nervous system (CNS). Here we studied how a dynamin‐2 CNM‐causing mutation influences the CNS function. Methods Heterozygous mice harbouring the p.R465W mutation in the dynamin–2 gene (HTZ), the most common causing autosomal dominant CNM, were used as disease model. We evaluated dendritic arborisation and spine density in hippocampal cultured neurons, analysed excitatory synaptic transmission by electrophysiological field recordings in hippocampal slices, and evaluated cognitive function by performing behavioural tests. Results HTZ hippocampal neurons exhibited reduced dendritic arborisation and lower spine density than WT neurons, which was reversed by transfecting an interference RNA against the dynamin‐2 mutant allele. Additionally, HTZ mice showed defective hippocampal excitatory synaptic transmission and reduced recognition memory compared to the WT condition. Conclusion Our findings suggest that the dynamin‐2 p.R465W mutation perturbs the synaptic and cognitive function in a CNM mouse model and support the idea that this GTPase plays a key role in regulating neuronal morphology and excitatory synaptic transmission in the hippocampus.

ABSTRACT The central regions of galaxies harbouring active galactic nuclei (AGNs) can be quite complex, especially at high activity, presenting, besides variability, a variety of phenomena related, e.g. to ionization/excitation mechanisms. A detailed study is necessary in order to understand better those objects. For that reason, we performed a multiwavelength analysis of the nuclear region of the nearby Seyfert galaxy NGC 7314, using an optical data cube obtained with the Integral Field Unit from the Gemini Multi-Object Spectrograph, together with Hubble Space Telescope images, X-ray data from the XMM–Newton and the Nuclear Spectroscopic Telescope Array and radio data from Atacama Large Millimeter/Submillimeter Array. The goals were to study the nuclear and circumnuclear emission, the emission of the AGN and the gas kinematics. The optical spectrum shows the emission of a Seyfert nucleus, with broad components in the H α and H β emission lines, characterising a type 1 AGN, with a spectrum rich in coronal emission lines. The spatial morphology of the [O iii] λ5007 suggests the presence of an ionization cone, west of the nucleus, meanwhile the east cone seems to be obscured by dust. An extended [Fe vii] λ6087 emission was also detected, which could be possibly explained by a scenario involving photoionization + shocks mechanisms. X-rays analyses showed that there are variations in the flux; however, we did not detect any variations in the column density along the line of sight. Its variability may be a consequence of changes in the AGN accretion rate.

Résumé Cet article rend compte d’un processus de recherche sur le champ des mathématiques au Chili, et en particulier sur la carrière des femmes dans le milieu scientifique, et l’ethos mathématicien. Ce projet a été mené à bien par une équipe de chercheur·e·s composée à parité de sociologues et mathématiciennes, ce qui constitue selon nous une expérience innovante d’interdisciplinarité. Nous l’abordons ici de façon réflexive, en la situant par rapport à la littérature sur l’interdisciplinarité et l’épistémologie féministe. Ensuite, nous présentons la méthodologie que nous avons mise en œuvre, celle des entretiens biographiques articulée à l’auto-ethnographie des mathématiciennes de l’équipe. Nous souhaitons enfin mettre en lumière les hiatus que cette collaboration interdisciplinaire a permis d’identifier, et les enseignements que nous en avons tiré quant à la constitution de l’ethos mathématicien.

Abstract An improved high-resolution and deep $A_{K_{s}}$ foreground dust extinction map is presented for the Galactic disc area within 295° ≲ l ≲ 350°, −1.0° ≲ b ≲ +1.0°. At some longitudes the map reaches up to |b| ∼ 2.25°, for a total of ∼148 deg2. The map was constructed via the Rayleigh–Jeans colour excess (RJCE) technique based on deep near-infrared (NIR) and mid-infrared (MIR) photometry. The new extinction map features a maximum bin size of 1 arcmin, and relies on NIR observations from the Two Micron All-Sky Survey (2MASS) and new data from ESO’s Vista Variables in the Vía Láctea (VVV) survey, in concert with MIR observations from the Galactic Legacy Infrared Mid-Plane Survey Extraordinaire. The VVV photometry penetrates ∼4 mag fainter than 2MASS, and provides enhanced sampling of the underlying stellar populations in this heavily obscured region. Consequently, the new results supersede existing RJCE maps tied solely to brighter photometry, revealing a systematic underestimation of extinction in prior work that was based on shallower data. The new high-resolution and large-scale extinction map presented here is readily available to the community through a web query interface.

Context. Hot subdwarfs are compact, evolved stars that serve as critical testbeds for understanding binary evolution, stellar remnants, and pulsation physics. Their formation is often attributed to binary interactions, but a significant fraction are apparently single, suggesting multiple formation pathways. Pulsating hot subdwarfs, whether in binaries or single, offer valuable opportunities for asteroseismic investigations to probe their internal structure and evolution. Aims. We aim to expand the known population of pulsating hot subdwarfs and explore their formation channels by investigating both binary and single systems. Methods. Using TESS light curves, we conducted a systematic variability search for hot subdwarf candidates identified from Gaia EDR3 and the TESS Input Catalogue. Variability was assessed using periodograms and applying a S/N > 5 threshold. Stars with multiple frequencies were classified as pulsators, while single-frequency sources were checked for binarity signatures such as harmonics or eclipses. Variability detections were verified with the TESS-Localize tool. Additionally, we performed follow-up spectroscopy for 11 targets, and carried out spectral energy distribution (SED) fitting to constrain the binary nature and fundamental stellar parameters. Results. We present 42 new variable hot subdwarfs, including 22 pulsators, 3 candidates for pulsating hot subdwarfs in binary systems (including one sdO star), and 13 additional binary candidates. The variability of 4 stars remains to be confirmed. Our spectroscopic and SED analyses of 11 stars provide improved constraints on stellar parameters and reveal new details about their binary nature. Conclusions. This work significantly expands the sample of known pulsating hot subdwarfs and binary candidates and demonstrates the importance of combined space-based photometry and ground-based follow-up in understanding the formation and evolution of hot subdwarf stars.

Hot subdwarf B (sdB) stars are evolved, subluminous, helium-burning stars that most likely form when red giant stars loose their hydrogen envelope via interactions with close companions. They play an important role in our understanding of binary evolution, stellar atmospheres, and interiors. Only a small fraction of the sdB population is known to exhibit pulsations. Pulsating sdBs have typically been discovered serendipitously in various photometric surveys because specific selection criteria for the sample are lacking. Consequently, while individual properties of these stars are well known, a comprehensive understanding of the entire population remains elusive, and many related questions remain unanswered. The Gaia mission has presented an exceptional chance to create an unbiased sample by employing precise criteria and ensuring a high degree of completeness. The progression of high-precision and high-duty cycle photometric monitoring facilitated by space missions such as Kepler /K2 and the Transiting Exoplanet Survey Satellite (TESS) has yielded an unparalleled wealth of data for pulsating sdBs. We created a dataset of confirmed pulsating sdB stars by combining information from various ground- and space-based photometric surveys. With this dataset, we present a thorough approach to search for pulsating sdB stars based on the current Gaia DR3 sample. Based on TESS photometry, we discovered 61 new pulsating sdB stars and 20 variable sdBs whose source of variability remains to be determined through future spectroscopic follow-up observations.

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society, © : 2016, J.S. Dunlop, et al, MNRAS (April 1, 2017) 466 (1): 861-883, first published online November 30, 2016, by Oxford University Press on behalf of MNRAS. The version of record is available on line at doi: 10.1093/mnras/stw3088

Nature-inspired metaheuristic algorithms, like Particle Swarm Optimization (PSO), are powerful general-purpose optimization tools but they invariably do not come with rigorous theoretical justifications and can fail to find a global optimum. By treating PSO as a random search optimization process and repairing the famous Global Search Convergence Theorem by imposing an additional condition in the proof, we create a novel theory-based algorithm called the Double Exponential Particle Swarm optimization algorithm (DExPSO) that converges to a global optimum. In particular, we show the common practice of using uniform variates as stochastic components in PSO and related algorithms does not satisfy the sufficient conditions in DExPSO and hence may provide a reason why PSO and other nature-inspired algorithms, like QPSO, LcRiPSO, and CSO can fail to converge. Additionally, in more complicated design problems, we show that DExpSO tends to converge to the support points of the optimal design more frequently and faster than PSO and its variants do. Moreover, there is a possibility to modify other PSO variants to DExPSO variants, and such hybridization offers promising improvement in the quality of the global search. Our applications include finding designs that minimize the integrated mean squared prediction error and locally D-optimal exact designs for a 68-compartmental model to assess radioactive particles retained in the human lung after exposure. Because PSO, and more generally, metaheuristics are used across disciplines, including ecology, pharmacokinetics and pharmacodynamics studies, agriculture, engineering, and computer science, there are potentially broad and deep implications of our results.

Large-pore channels allow the exchange of ions and molecules between the intra- and extracellular compartments. These channels are structures formed by several protein families with little or no evolutionary linkages that include connexins (Cxs), pannexins (Panxs), innexins (Inxs), CALHM1, and LRRC8 proteins. Recently, we have described the unnexins (Unxs) proteins expressed in Trypanosoma cruzi (T. cruzi) that also is like to form large-pore channels at the plasma membrane. In this chapter, we describe a dye uptake method for evaluating the unnexin-formed channel function in T. cruzi, as well as the methods for evaluating their participation in the transformation of trypomastigotes into amastigotes. These methods can facilitate understanding the role of large-pore channels in the parasite’s biology.